A single-section deconvolution-derived computerized tomographic perfusion imaging was performed in 45 patients (22 male and 23 female; mean age=69.89±10.07 years) with acute supratentorial spontaneous intracerebral hemorrhage. Mean rCBF and rCBV were lower in the hemorrhagic core than in the perihematomal low density area (p≪0.001), and in the perihematomal low density area than in normal appearing brain parenchyma (p≪0.001). Mean rMTT values were higher in perihematomal low density area than in normal appearing area (p≪0.01) and in both hemorrhagic and perihematomal area than in controlateral ROI (p≪0.001). There were no differences in rMTT mean values between hemorrhagic core and perihematomal area, as well as between normal appearing and controlateral areas. We found a concentric distribution of all CT perfusion parameters characterized by an improvement from the core to the periphery, with low perihematomal rCBF and rCBV values suggesting edema formation.

Several efforts have previously been made to verify whether in the region peripheral to hematoma there exists a zone of ischemic penumbra, defined as severely hypoperfused tissue at risk for infarction which is functionally compromised but structurally intact and, therefore, still viable and salvageable if blood flow is rapidly restored [6Heiss W-D. Ischemic penumbra: evidence from functional imaging in man. J Cereb Blood Flow Metab 2000; 20: 1276-1293.

Click here to see the Library]. Based on these considerations and in an attempt to provide further insight into the assessment and the distribution of lesional and perilesional perfusion alterations, we sought to quantify CBF changes within and around acute SICH by using deconvolution-derived CT perfusion hemodynamic imaging.

We recruited in the study 45 patients with acute supratentorial SICH on unenhanced admission CT scans carried out within 24 hours of symptomatic onset. Time of onset was considered as the last time the patient was known to be neurologically normal. Patients with infratentorial hemorrhage, hematoma related to tumor, trauma, coagulopathy, aneurysms, vascular malformations, hemorrhagic transformation of brain infarction, intraventricular extension of hemorrhage and patients who had undergone surgical hematoma evacuation were excluded. Disease severity was scored in all patients at entry using Glasgow Coma Scale (GCS) [22Teasdale G, Jennet B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974; 2: 81-84.

CT perfusion examinations were performed by using a single-section CT scanner (CT HiSpeed ZX/i; GE Healthcare, Milwaukee, Wis) equipped for CT perfusion imaging (CT Perfusion; GE Healthcare, Milwaukee, Wis). After hematoma localization on unenhanced CT scanning, the imaging protocol for CT perfusion consisted of a series of 45 CT scans acquired in a single slice (10-mm slice thickness, 80kVp; 200mAs; matrix 512×512; FOV 25-cm; total scan time 50sec) located at the hematoma level during the automatic injection of 50ml of non-ionic contrast agent at the rate of 3.5ml/sec, starting 5 seconds before the initial image. The reference image on non-contrast CT scans was selected on the basis of the level containing the largest volume of blood. All CT perfusion scans were assessed with a deconvolution-based algorithm by using an imaging workstation (Advantage Windows; GE Medical System, Milwaukee, Wis) supplied with a commercial dedicated software (CT Perfusion 2, GE Healthcare, Milwaukee, Wis). CBF, CBV and MTT perfusion maps were generated for each patient. As illustrated in figure 1, regional CBF (rCBF), CBV (rCBV) and MTT (rMTT) levels were measured in three different regions of interest (ROIs) larger than 1cm2 and manually outlined on the baseline single slice CT scan and including: 1) hemorrhagic core; 2) perihematomal low density area; 3) 1cm rim of normal appearing brain tissue surrounding the perilesional low density area. An additional ROI that mirrored the region including the clot and perihematomal low density area was placed in the contralateral hemisphere. CBF, CBV and MTT values were expressed in ml/100g/min, ml/100g and seconds, respectively. rCBF values lower than 10 ml/100g/min, ranging from 10 to 20ml/100g/min, and included between 20 and 40ml/100g/min were considered as ischemic, penumbral and oligemic, respectively [5Furlan M, Marchal G, Viader F, Derlon J-M, Baron J-C. Spontaneous neurological recovery after stroke and fate of ischemic penumbra. Ann Neurol 1996; 40: 216-226.

Mann-Whitney U test was used to compare mean values among the various groups. The Spearman rank correlation coefficient test was used to identify possible relationships among the different variables. Statistical significance was set at p≪0.05.

Demographic and clinical features of the 45 patients included in the study are listed in the table I. Overall, mean hematoma volume was 18.38±25.32 (range=0.72-129.25), whereas the mean time from symptom onset and CT perfusion scanning was 10.10±4.90 hours (range=2.44-21.24 hours; median=9.42 hours).

CT perfusion measurements

Mean rCBF and rCBV levels were significantly lower in hemorrhagic core (10.308±6.851ml/100g/min and 0.828±0.456ml/100g, respectively) than in perihematomal low density area (34.506±15.784ml/100g/min and 2.25±0.927ml/100g, respectively) (p≪0.001), and in perihematomal area than in normal appearing area (68.779±52.393ml/100g/min and 3.692±2.349ml/100g, respectively) and contralateral ROI (68.158±35.021ml/100g/min and 3.675±1.651ml/100g, respectively) (p≪0.001). rCBF and rCBV mean levels were similar in normal appearing and contralateral area. Mean rMTT values were significantly higher in both hemorrhagic core and perihematomal area (5.507±1.832 and 5.74±1.245 seconds, respectively) than in normal appearing area (4.542±0.973 seconds) (p≪0.01) and contralateral ROI (4.53±0.796 seconds) (p≪0.001). There were no differences in rMTT mean values between hemorrhagic core and perihematomal area, as well as between normal appearing and contralateral areas. Interestingly, when we evaluated absolute mean values of each perfusion parameter, rCBF levels approached irreversible ischemic levels in hemorrhagic core, while they were oligemic in perihematomal low density area and hyperperfusional in both normal appearing and contralateral areas. rCBV levels were decreased only in hemorrhagic core, whereas none of the ROI examined showed rMTT abnormal levels.

Correlations between perfusion parameters and hematoma volume

In acute SICH patients, rCBF and rCBV mean levels and hematoma volume were inversely and significantly correlated (r=–0.500 and r=–0.589, respectively; p≪0.001) in hemorrhagic core. A negative significant correlation was also seen between rCBF and rCBV mean levels and hematoma volume (r=–0.453 and r=–0.423, respectively; p≪0.01) in perihematomal area.

Click here to see the Library], we found that perfusional parameters were concentrically distributed and gradually improved from the core to the periphery but we did not observe zero-flow values within the hemorrhagic core having rCBV at severe ischemic levels, but rCBF and rMTT values which were only close to the threshold of irreversible tissue damage. This apparent paradox may be due to the presence of a thin peripheral border with residual flow and relatively preserved CBV and MTT surrounding the central part of the hemorrhagic core with no flow. This outer band, probably reflecting penumbral tissue evolving into infarction [6Heiss W-D. Ischemic penumbra: evidence from functional imaging in man. J Cereb Blood Flow Metab 2000; 20: 1276-1293.

Click here to see the Library], no evidence of ischemic penumbra was identified in perihematomal low density area where CBF levels were largely indicative of oligemic tissue not at risk for infarction. More precisely, the concomitant decrease of rCBF and rCBV detected in this area seems to suggest the development of brain edema [16Muizelaar JP, Fatouros PP, Schröder ML. A new method for quantitative regional cerebral blood volume measurements usimg computed tomography. Stroke 1997; 28: 1998-2005.

Click here to see the Library]. These findings appear to be concordant with data coming from animal investigations reporting that perihematomal edema formation is mediated by the clotting of intrahematoma blood with liberation of the remaining serum proteins, especially thrombin, into the surrounding brain parenchyma [11Lee KR, Colon GP, Betz AL, Keep RF, Kim S, Hoff JT. Edema from intracerebral hemorrhage: the role of thrombin. J Neurosurg 1996; 84: 91-96.

Click here to see the Library] we found hyperperfusional levels that were not associated to a decrease in rCBV and rMTT values are of particular relevance as they most likely indicate luxury perfusion or abnormal vasodilatation [14Marchal G, Young AR, Baron J-C.Early postischemic hyperperfusion: pathophysiologic insights from positron emission tomography. J Cereb Blood Flow Metab 1999; 19: 467-482.

Click here to see the Library]. The main limitations of the study were the inclusion of large blood vessels in CBF calculation that could lead to an overestimation of CBF values [10Kudo K, Terae S, Katoh C, Oka M, Shiga T, Tamaki N, Myasaka K. Quantitative cerebral blood flow measurement with dynamic perfusion CT using the vascular pixel elimination method: comparison with H215O positron emission tomography. AJNR Am J Neuroradiol 2003; 24: 419-426.

Click here to see the Library] and the restriction of the brain coverage to a single section. However, the first-pass bolus-tracking CT perfusion methodology and the accuracy of the deconvolution process have been validated [3Cenic A, Nabavi DG, Craen RA, Gelb AW, Lee TY. Dynamic CT measurement of cerebral blood flow: a validation study. AJNR AmJ Neuroradiol 1999; 20: 63-73.

Click here to see the Library], and the advent of multisclice CT scanners could overcome the limited extension of the perfusion analysis. Collectively taken, our findings suggest that dynamic CT perfusion scanning with deconvolution analysis is a powerful method for the evaluation of perfusion deficits associated with acute SICH. They further indicate that perfusion parameters are concentrically distributed and gradually improve from the core to the periphery. In addition, no evidence of ischemic penumbra was found in perihematomal area with rCBF and rCBV levels arguing for oligemia and edema formation. Finally, hyperperfusion values were observed in normal appearing brain tissue located both ipsilaterally and contralaterally to hematoma.

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